Editor's Commentary - Risk stratification and validation of prostate specific antigen density as independent predictor of progression in men with low risk prostate cancer during active surveillance

BERKELEY, CA (UroToday.com) - A subset of patients with low-risk prostate cancer (CaP) will undergo Active Surveillance (AS) rather than immediate treatment. This is due to the lead-time bias in the detection of their prostate cancer and the low likelihood of disease progression. However, about one-third will progress over a 10-year period. Parameters that best identify patients at risk for progression are critical. Presently, serial prostate biopsies at one to two year intervals are probably the best way to identify progression, and PSADT is another parameter although not shown by all groups to be as significant. In the February, 2011 edition of the Journal of Urology, Dr. Ignacio San Francisco and colleagues report a risk stratification approach to AS patients.

The group studied a total of 135 consecutive patients entered into an AS protocol from Jan 2000 through February 2010. All men had stage T1c-T2c disease, Gleason score 6 or less tumors with no pattern 4, 3 cores or less involved with CaP and no more than 50% cancer in any core. PSA or PSA derivatives were not used in the criteria. A confirmatory 20-core prostate biopsy was performed to evaluate for undergrading or staging of the cancer. Patients were followed every 6 months with a PSA and DRE and a 20- core biopsy every 12-18 months. Progression leading to a recommendation of active treatment included increase in Gleason score to 7 or higher, 3 or more cores positive with CaP or more than 50% of any core involved with cancer.

Median followup was 2.4 years and 120 patients had at least one re-biopsy. Only 57 patients had at least 2 biopsies. Thirty-six of 120 men had progression on re-biopsy (30%). Of the 36 patients with progression, 21, 6, 8, and 1 progressed at the first, second, third and fourth re-biopsy, respectively. The investigators report that an estimated 17%, 26%, 43%, 48%, and 48% of men had progression by re-biopsy 1 to 5, respectively. An estimated 28% of men progressed by year 3 and 67% of men by year 6. The most common cause of progression by criteria was number of cores with CaP in 18 of 36 men, Gleason score progression in 11 and a combination of these two in 6 patients. The researchers did two multivariate models. The first involved clinical and pathological variables only at diagnostic biopsy. Men with a PSAD at diagnosis above the median (greater than 0.08ng/ml/cc) were more likely to experience disease progression on re-biopsy than those below this value. Those with a family history of CaP were more likely to experience progression than those without (HR 1.93). A 2-variable risk factor score was developed combining these two variables (possible score of 0, 1, or 2). Patients with both a high PSAD and positive family history (risk score of 2) were more likely to have progression (HR 5.10 compared to a score of 0). A score of 1 vs. 0 resulted in an HR of 2.29. The second model added in PSAV as well and a rapidly increasing PSAV between diagnosis and re-biopsy resulted in greater likelihood of progression (HR 2.82). Thus a risk score including all three variables (scores 0-3) was the best. A score of 3 vs. 0 resulted in an HR of 19.49.

San Francisco IF, Werner L, Regan MM, Garnick MB, Bubley G, Dewolf WC

J Urol. 2011 Feb;185(2):471-6
10.1016/j.juro.2010.09.115

PubMed Abstract
PMID: 21167525

UroToday.com Prostate Cancer Section

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